The pre-menstrual syndrome (PMS) in women is a medical condition characterized by a number of both somatic and psychological symptoms. The condition first was described by Frank, Arch. Neurol. Psychiatr. 26:1053 (1931). The symptoms of PMS are associated with a woman's menstrual cycle and appear only during that portion of her menstrual cycle which follows ovulation. Thus, PMS is a syndrome of the luteal phase of the menstrual cycle.
PMS is a chronic condition, and women who suffer from it typically experience it with each cycle during the fertile phases of their lives, i.e., between the first menstrual cycle (the menarche) and the last menstrual cycle, a period of time after which a woman enters menopause. Fluctuations from cycle to cycle in the severity of PMS frequently occur, however, with some months being associated with significantly more difficulties than others. The intensity of the manifestations of the syndrome also can vary from year to year, as a woman passes through different phases in her reproductive life.
Typically, a woman ovulates each month during the reproductive phase of her life. Thus, PMS can be a significant disability for many years of a woman's life. PMS has a profound effect on the working capacity of afflicted women and can cause the loss of many days of work over a woman's lifetime. It has been estimated that the cost of lost working days due to PMS in the United States alone exceeds ten billion dollars annually. In addition, PMS can lead to marital and family problems and cause intense suffering on the part of those who suffer from it.
As noted above, the timing of symptoms of PMS coincides with a certain part of a woman's menstrual cycle. Typically, the condition is manifested after ovulation (i.e., during the luteal phase of the menstrual cycle) and is intensified as the woman approaches the onset of menstruation. Most commonly, the symptoms are most pronounced during the last seven to ten days of the luteal phase of her cycle, that is, the last seven to ten days prior to the onset of her menstrual bleed. Once the menstrual blood loss has begun, the symptoms abate and the condition of the patient improves.
The most common somatic symptoms of PMS include swelling and tenderness of the breasts, abdominal pain, pelvic pain and cramps, pain in the iliac fossa, feelings of bloatedness and weight gain, diminished activity, efficiency and performance, perspiring, skin lesions, edema, vertigo and diarrhea or constipation. Less common symptoms include sore eyes, joint pain, asthma and epilepsy.
The most common psychological symptoms include irritability, agitation, anxiety, confusion, fatigue, mental depression, lethargy, insomnia or hypersomnia, decreased libido, loss of confidence and judgment, suicidal ideation, accident proneness, loss of concentration and attention span and the development of food cravings, especially for sweets, such as chocolate.
The combination of the somatic and psychological symptoms which can be experienced by one suffering from PMS can lead to social isolation, a poor ability to function in the workplace and home and difficulties in relating to family members
According to some physicians, PMS best can be classified as a number of distinct subsyndromes dependent upon the clustering of symptoms characteristic of the classified subject. See Abraham, J. Reproductive Med. 32(6):405 (1987). In this system of classification of PMS (termed PMTS for pre-menstrual tension syndromes) the following subtypes exist:
(a) PMT-A: symptoms primarily include anxiety, irritability and nervous tension, which progress in time from mid-cycle to menstruation and frequently are associated with a depressive mood change.
(b) PMT-H: predominant symptoms include premenstrual sensation of weight gain, abdominal bloating and tenderness, breast congestion and mastalgia and occasionally, minimal edema.
(c) PMT-C: in this subgroup, the primary symptom is an increased appetite in the luteal phase of the menstrual cycle. The food craving and hunger primarily are directed toward refined sugars. The food craving frequently is associated with emotional tension.
(d) PMT-D: this subsyndrome primarily is characterized by intense states of confusion, social withdrawal and suicidal ideation. The patients also may experience shifts in their energy levels, with some becoming lethargic and others becoming very excitable. Many of these patients complain of difficulties in verbalization.
The etiology of PMS is not well understood. A number of conflicting theories have been proposed to explain the condition. Despite fifty years of intensive research, however, most authorities agree that no definitive etiology and pathophysiology have been elucidated for this complex physical condition.
In view of the fact that PMS is associated with the menstrual cycle, many theories are based on the assumption that the condition is related to a basic "endocrine imbalance" in the women who suffer from the syndrome. Attention has been focused especially upon ovarian hormones. Some scientists have considered a progesterone deficiency to play a role in PMS, while others have related the condition to an excess of estrogens or androgens. Others have thought the endocrinological aberration to be related to adrenal cortex hormones, such as corticosteroid (hydrocortisone) or mineral corticoids (aldosterone).
In yet other theories, mastalgia and fluid retention were thought to be related to pituitary dysfunction and specifically to an excessive secretion of the hormone prolactin. Some studies have considered the basic dysfunction associated with PMS to be related to prostaglandin secretion and metabolism. Other theories have considered a serotonin deficiency syndrome and a hypothesized "neuro-endocrine imbalance."
Other scientists have related PMS to a nutritional deficiency in either vitamin B-complex, especially vitamin B-6 (pyroxidine), or essential fatty acids, especially linolenic acid. Others have put forth the "yeast overgrowth syndrome" which was thought to be the outcome of pu candida albicans' overgrowth with associated production of "toxins." Some additional studies have looked for various food allergies and respiratory allergies as an explanation of PMS.
Reviews summarizing these various theories include O'Brien, P., J. Reprod. Med. 30(2): 113 (1985); Claire, A., Canadian J Psych. 30(7):474 (1985); Bancroft, J. and T. Bachstrom, Clin. Endocrin. 22:313 (1985); Abraham, G. E., J. Reprod. Med. 28(7):433 (1987); and Abraham, G. E., J. Reprod. Med. 32(6):387 (1987).
Despite all these efforts, no definite etiology has been determined. As a result, treatment of PMS has taken numerous forms and has reflected the wide variety of theories of its cause. Most commonly, the treatment of PMS has been treated through the administration of nonsteroidal, anti-inflammatory drugs, including aspirin, naparoxen, indomethacin, mefenamic acid, ibuprofen and piroxicam. See Shapiro, S. S. Druqs 36:475 (1988).
In other treatment modalities, physicians have prescribed psychoactive drugs, such as lithium carbonate, benzodiazepines, and tricyclic antidepressants, and frequently have combined them with intensive psychiatric treatment.
Still other treatment modalities have been focused on efforts to correct the poorly understood "endocrine imbalance" through the administration of various contraceptive medication combinations. Unfortunately, however, many women have reported that taking the oral contraceptives have made them feel worse. See Cullberg, J. Acta Psychiatr. Scand. 236(supp. 1):1 (1972). Other endocrine treatments have involved the administration of progesterone in the luteal phase of the menstrual cycle; for example, 100 mg progesterone administered each morning and 200 mg administered each evening have been found to have a significant benefit for women with PMS. See Dennerstein et al., Br. Med. J. (Clin. Res.) 290(6482): 1617 (1985). In other treatments, depot methoxyprogesterone has been administered and reported to be effective. Treatment with progesterone has a limited value, however, in that most of the symptoms of PMS do not disappear upon its administration.
Other treatment methods that have been tried include endocrine management of the condition through the treatment with thyroid hormone medication; bromocriptine administration to reduce the synthesis and secretion of prolactin; and danazol administration to inhibit multiple enzymes involved in ovarian steroidogenesis and prevent the midcycle LH surge. This last method of treatment is effective in some patients; however, it carries with it the risk of estrogen withdrawal and early climacteric symptoms. It also can cause osteoporosis in long term users.
In view of the drawbacks and inadequacies with existing methods of treating PMS, new therapies are sought. Accordingly, it is an object of the present invention to provide a method for effectively alleviating the symptoms of PMS. It is a further object of this invention to provide such a method that is attended by a minimum of negative side effects.